The goal of this proposal is to describe and evaluate the criteria necessary for the use of enzyme inhibitors as radiopharmaceutical agents. This proposal focuses on metyrapone and the 11Beta-hydroxylase enzyme system as a model system for this evaluation. Metyrapone is an inhibitor of 11Beta-hydroxylase activity and binds to the cytochrome P-450 of this enzyme system. Since 11Beta-hydroxylase is found almost exclusively in the adrenal cortex and the interaction of metyrapone appears to be selective for this enzyme system in vitro, analogs of metyrapone may have the best potential for being selective inhibitors of 11Beta-hydroxylase and radiolabeled analogs of metyrapone may have the best potential for being selective radiopharmaceutical agents of the adrenal cortex. The specific objectives of this proposal are to design, synthesize, and evaluate the biochemicstry and radiopharmacology of a series of metyrapone analogs. Structure activity relationship studies will be done with each proposed analog in vitro to evaluate the potential and selective inhibition of 11Beta-hydroxylase. Active compounds will be evaluated in tissue distribution studies by both in vivo uptake and enxyme inhibition with respect to time and dosage. Since the ultimate goal is to develop imaging agents, these studies may be of clinical value especially for understanding the potential and limitations of enzyme inhibitors as a principle of radiopharmaceutical design.